Phase 2b Study of PTC124 in Duchenne/Becker Muscular Dystrophy (DMD/BMD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics
ClinicalTrials.gov Identifier:
NCT00592553
First received: January 1, 2008
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

Duchenne/Becker muscular dystrophy (DMD/BMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of DMD/BMD in approximately 10-15% of boys with the disease. PTC124 is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2b trial that will evaluate the clinical benefit of PTC124 in boys with DMD/BMD due to a nonsense mutation. The main goals of the study are to understand whether PTC124 can improve walking, activity, muscle function, and strength and whether the drug can safely be given for a long period of time.


Condition Intervention Phase
Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
Drug: PTC124
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b Efficacy and Safety Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne Muscular Dystrophy and Becker Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:
  • To determine the effect of PTC124 on ambulation in subjects with nonsense-mutation-mediated DMD/BMD (as assessed by changes in the distance walked during a 6-minute walk test) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Activity in the community setting [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Proximal muscle function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Muscle strength [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Muscle fragility [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Biceps muscle dystrophin expression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Cognitive ability [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Cardiac function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Frequency of accidental falls during ambulation [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Treatment satisfaction [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Compliance with treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • PTC124 pharmacokinetics [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 174
Study Start Date: February 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: PTC124
PTC124 Low Dose
Active Comparator: 2 Drug: PTC124
PTC124 High Dose
Placebo Comparator: 3 Drug: PTC124
Placebo

Detailed Description:

This study is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, efficacy and safety study, designed to document the clinical benefit of PTC124 when administered as therapy of patients with DMD/BMD due to a nonsense mutation (premature stop codon) in the dystrophin gene. It is planned that ~165 boys who are at least 5 years of age and can walk at least 75 meters (80 yards) will be enrolled. Study subjects will be enrolled at sites in North America, Europe, Israel, and Australia. They will be randomized in a 1:1:1 ratio to either a higher dose of PTC124, a lower dose of PTC124, or placebo. Subjects will receive study drug 3 times per day (at breakfast, lunch, and dinner) for 48 weeks. Subjects will be evaluated at clinic visits every 6 weeks. Additional safety laboratory testing, which may be performed at the investigational site or at an accredited local laboratory or clinic, is required every 3 weeks for the first 24 weeks of the study. At the completion of blinded treatment, all compliant participants will be eligible to receive open-label PTC124 in a separate extension study.

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age)
  • Male sex.
  • Age ≥5 years.
  • Phenotypic evidence of DMD/BMD based on the onset of characteristic clinical symptoms or signs (ie., proximal muscle weakness, waddling gait, and Gowers' maneuver) by 9 years of age, an elevated serum creatinine kinase level, and ongoing difficulty with walking.
  • Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an equivalent organization.
  • Ability to walk ≥75 meters unassisted during the screening 6-minute walk test.
  • Documentation that a baseline renal ultrasound has been performed.
  • Confirmed screening laboratory values within the central laboratory ranges (adrenal, renal, and serum electrolytes parameters)
  • Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

  • Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
  • Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or change in systemic corticosteroid therapy (eg, initiation, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, discontinuation, or reinitiation) within 3 months prior to start of study treatment.
  • Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure within 3 months prior to start of study treatment.
  • Treatment with warfarin within 1 month prior to start of study treatment.
  • Prior therapy with PTC124.
  • Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).
  • Exposure to another investigational drug within 2 months prior to start of study treatment.
  • History of major surgical procedure within 30 days prior to start of study treatment.
  • Ongoing immunosuppressive therapy (other than corticosteroids).
  • Ongoing participation in any other therapeutic clinical trial.
  • Expectation of major surgical procedure (eg, scoliosis surgery) during the 12 month treatment period of the study.
  • Requirement for daytime ventilator assistance.
  • Clinical symptoms and signs of congestive heart failure (American College of Cardiology/American Heart Association Stage C or Stage D) or evidence on echocardiogram of clinically significant myopathy
  • Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00592553

  Hide Study Locations
Locations
United States, California
University of California-Davis
Sacramento, California, United States
United States, Colorado
The Children's Hospital
Aurora, Colorado, United States
United States, Florida
Child Neurology Center of Pensacola
Pensacola, Florida, United States
United States, Iowa
University of Iowa Healthcare
Iowa City, Iowa, United States
United States, Kansas
University of Kansas Medical Centre
Kansas City, Kansas, United States
United States, Massachusetts
Children's Hospital of Boston/Harvard Medical School
Boston, Massachusetts, United States
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States
United States, New York
Columbia University Medical School
New York City, New York, United States
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Oregon
Shriners Hospital for Children
Portland, Oregon, United States
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
United States, Texas
Southwestern University
Dallas, Texas, United States
United States, Utah
University of Utah
Salt Lake City, Utah, United States
Australia
Royal Children's Hospital
Parkville, Victoria, Australia
Institute For Neuromuscular Research, The Children's Hospital at Westmead
Westmead, Australia
Belgium
University Hospital KU Leuven
Leuven, Belgium
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
Canada, Ontario
London Health Sciences Center
London, Ontario, Canada
France
Service de Neuropediatrie, hôpital La Timone
Marseille, France
Neuromuscular center of Nantes
Nantes, France
Groupe Hospitalier La Pitie-Salpetriere
Paris, France
Germany
University Clinic for Children, University of Essen
Essen, Germany
University Hospital
Freiburg, Germany
Israel
Hadassah Medical Center, Hebrew University Hospital
Jerusalem, Israel
Italy
Ospedale Maggiore Policlinico in Milan
Milan, Italy
Ospedale Pediatrico Bambino Gesu
Rome, Italy
U.O. Complessa di Neuropsichiatria Infantile
Rome, Italy
Spain
Hospital Sant Joan de déu
Barcelona, Spain
Hospital Universitari La Fe
Valencia, Spain
Sweden
Queen Silvia Children's Hospital
Goteburg, Sweden
Astrid Lindgren Pediatric Hospital
Stockholm, Sweden
United Kingdom
Imperial College London, Hammersmith Hospital
London, United Kingdom
Univ of Newcastle, Institute of Human Genetics
Newcastle, United Kingdom
Robert Jones and Agnes Hunt Orthopaedic NHS Trust
Shropshire, United Kingdom
Sponsors and Collaborators
PTC Therapeutics
Investigators
Study Director: Leone Atkinson, MD, PhD PTC Therapeutics
  More Information

No publications provided

Responsible Party: PTC Therapeutics
ClinicalTrials.gov Identifier: NCT00592553     History of Changes
Other Study ID Numbers: PTC124-GD-007-DMD
Study First Received: January 1, 2008
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by PTC Therapeutics:
Duchenne muscular dystrophy
Becker muscular dystrophy
Nonsense mutation
Premature stop codon
DMD/BMD
PTC124

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on August 28, 2014